The heart is a pump which pumps blood throughout the body. It consists of four chambers, including a left atrium, a right atrium, a left ventricle and a right ventricle. In order for the heart to efficiently perform its function as a pump, the atrial muscles and ventricular muscles should contract in a proper sequence and in a timed relationship.
In a given cardiac cycle (corresponding to one “beat” of the heart), the two atria contract, forcing the blood therein into the ventricles. A short time later, the two ventricles contract, forcing the blood therein to the lungs (from the right ventricle) or through the body (from the left ventricle). Meanwhile, blood from the body fills the right atrium and blood from the lungs fills the left atrium, waiting for the next cycle to begin. A typical healthy adult heart can beat at a rate of 60-70 beats per minute (bpm) while at rest, and can increase its rate to 140-180 bpm when the adult is engaging in strenuous physical exercise, or undergoing other physiologic stress.
The healthy heart controls its rhythm from its sino-atrial (SA) node, located in the upper portion of the right atrium. The SA node generates an electrical impulse at a rate commonly referred to as the “sinus” rate. This impulse is delivered to the atrial tissue when the atria are to contract and, after a suitable delay, propagates to the ventricular tissue when the ventricles are to contract.
When the atria contract, a detectable electrical signal referred to as a P-wave is generated. When the ventricles contract, a detectable electrical signal referred to as the QRS complex (also referred to simply as an “R-wave”) is generated, as a result of the depolarization of the ventricles. The R-wave is much larger than the P-wave, principally because the ventricular muscle tissue is much more massive than the atrial muscle tissue. The atrial muscle tissue need only produce a contraction sufficient to move the blood a very short distance, from the respective atrium to its corresponding ventricle. In contrast, the ventricular muscle tissue must produce a contraction sufficient to push the blood over a longer distance (e.g., through the complete circulatory system of the entire body).
It is the function of a pacemaker to provide electrical stimulation pulses to the appropriate chamber(s) of the heart (atria and/or ventricles) in the event the heart is unable to beat on its own (e.g., in the event either the SA node fails to generate its own natural stimulation pulses at an appropriate sinus rate, or in the event such natural stimulation pulses do not effectively propagate to the appropriate cardiac tissue). Most modern pacemakers accomplish this function by operating in a “demand” mode where stimulation pulses from the pacemaker are provided to the heart only when it is not beating on its own, as sensed by monitoring the appropriate chamber of the heart for the occurrence of a P-wave or an R-wave. If a P-wave or an R-wave is not sensed within a prescribed period of time (which period of time is often referred to as the “escape interval”), then a stimulation pulse is generated at the conclusion of this prescribed period of time and delivered to the appropriate heart chamber via a pacemaker lead.
Modern programmable pacemakers are generally of two types: (1) single chamber pacemakers, and (2) dual-chamber pacemakers. In a single chamber pacemaker, the pacemaker provides stimulation pulses to, and senses cardiac activity within, a single-chamber of the heart (e.g., either the right ventricle or the right atrium). In a dual-chamber pacemaker, the pacemaker provides stimulation pulses to, and senses cardiac activity within, two chambers of the heart (e.g., both the right atrium and the right ventricle). The left atrium and left ventricle can also be paced, provided that suitable electrical contacts are made therewith.
Atrial fibrillation (AF) is a characterized by an abnormal heart rhythm in which the atria, or upper chambers of the heart, ‘quiver’ chaotically and the ventricles beat irregularly, where the resulting heartbeat is completely irregular. In AF, the atrial muscles contract very quickly and irregularly; while the ventricles beat irregularly but not as fast as the atria. When the atria fibrillate, blood that is not completely pumped out can pool and form a clot, which can lead to a stroke if the clot is carried by the blood flow to the brain. According to the American Heart Association, AF is the most common chronic arrhythmia, afflicting nearly 2 million Americans. The prevalence of AF increases with age and is slightly more common in men than in women. AF is responsible for about 15% of strokes. Often, AF begins with short episodes of palpitations or a fluttering sensation in the chest. Over time, there is a tendency for these episodes to become longer. Once AF has been initiated, the atria undergo a process known as ‘remodeling’. AF-induced atrial remodeling causes both structural and electrical changes. AF is usually diagnosed through electrocardiography (ECGs), an exercise stress test, a 24-hour Holter ECG monitor, or a telephone cardiac monitor. AF is usually treated with medications and/or electrical shock (cardio version). In some cases, removal of a small portion of the heart (ablation), implantation of a pacemaker or a cardioverter defibrillator is required.
Atrial anti-tachycardia pacing (AATP) is a standard treatment option to terminate most re-entrant tachycardia. Although AATP is very effective on atrial flutter termination (with success in terminating atrial flutter in >80% of cases), AATP is very ineffective on atrial fibrillation (AF) termination (with success in terminating AF in <20% of cases). Recent studies have demonstrated that dual-site right atrial pacing decreases the recurrence of AF and that dual-site bi-atrial pacing decreases the inducibility of AF in patients. However, chronic dual-site atrial pacing alone has proven disappointing in long-term clinical trials.
Neurostimulation of atrial fat pads and/or parasympathetic neural inputs to them has been shown to modulate the SA rate, AV conduction, the atrial effective refractory period (AERP), and its homogeneity across both atria. In particular, tonic neural activity of the atrial fat pads leads to shortening of the AERP and increases the heterogeneity of refractoriness throughout the atria. Neurostimulation to the coronary sinus region adjacent to the AV nodal fat pad can be used to achieve AV nodal block using high frequency, narrow pulses. However the stimulation levels required to achieve AV block are so high that patients report “pain”. Lower levels of stimulation that are not perceived as painful generally don't produce enough AV slowing to be considered an effective therapy for atrial fibrillation (AF).